Pretranscriptional regulation of Tgf-beta1 by PI polyamide prevents scarring and accelerates wound healing of the cornea after exposure to alkali.

ABSTRACT: Corneal alkali burns are a serious clinical problem that often leads to permanent visual impairment. In this process, transforming growth factor (Tgf)-beta1 is upregulated and involved in the response to corneal injury and the process of corneal stromal scarring. To develop an efficient compound to inhibit Tgf-beta1 in the cornea, we designed GB1201, a pyrrole-imidazole (PI) polyamide targeting rat Tgf-beta1 gene promoter to the activator protein-1 (AP-1) binding site. GB1201 showed a high binding affinity to the target DNA sequence in the gel mobility shift and Biacore assays. GB1201 significantly inhibited the rat Tgf-beta1 gene promoter activity in HEK (human embryonic kidney) 293 cells in a concentration-dependent manner. Topically administrated GB1201 was distributed immediately to th

SUBMITTER: Chen M 

PROVIDER: S-EPMC2839444 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature